title: HCN1 subunits contribute to the kinetics of I(h) in neonatal cortical plate neurons.
abstract: The distribution of ion channels in neurons regulates neuronal activity and proper formation of neuronal networks during neuronal development. One of the channels is the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel constituting the molecular substrate of hyperpolarization-activated current (I(h)). Our previous study implied a role for the fastest activating subunit HCN1 in the generation of Ih in rat neonatal cortical plate neurons. To better understand the impact of HCN1 in early neocortical development, we here performed biochemical analysis and whole-cell recordings in neonatal cortical plate and juvenile layer 5 somatosensory neurons of HCN1(-/-) and control HCN1(+/+) mice. Western Blot analysis revealed that HCN1 protein expression in neonatal cortical plate tissue of HCN(+/+) mice amounted to only 3% of the HCN1 in young adult cortex and suggested that in HCN1(-/-) mice other isoforms (particularly HCN4) might be compensatory up-regulated. At the first day after birth, functional ablation of the HCN1 subunit did not affect the proportion of Ih expressing pyramidal cortical plate neurons. Although the contribution of individual subunit proteins remains open, the lack of HCN1 markedly slowed the current activation and deactivation in individual I(h) expressing neurons. However, it did not impair maximal amplitude/density, voltage dependence of activation, and cAMP sensitivity. In conclusion, our data imply that, although expression is relatively low, HCN1 contributes substantially to I(h) properties in individual cortical plate neurons. These properties are significantly changed in HCN1(-/-), either due to the lack of HCN1 itself or due to compensatory mechanisms.
authors.affiliation: Institute of Cell Biology & Neurobiology, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Luminita
authors.initials: L
authors.lastname: Stoenica
authors.forename: Wiebke
authors.initials: W
authors.lastname: Wilkars
authors.forename: Arne
authors.initials: A
authors.lastname: Battefeld
authors.forename: Konstantin
authors.initials: K
authors.lastname: Stadler
authors.forename: Roland
authors.initials: R
authors.lastname: Bender
authors.forename: Ulf
authors.initials: U
authors.lastname: Strauss
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000378:metabolism; D005260:Female; D055786:Gene Knockout Techniques; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000378:metabolism*; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology*; D051379:Mice; D057507:Mice, 129 Strain; D009474:Neurons / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D017966:Pyramidal Cells / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; C578666:Hcn1 protein, mouse; C578667:Hcn1 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels
keywords: current kinetics; hyperpolarization-activated current; neocortex; neural development; patch-clamp